The objectives of this project are the development, evaluation, and utilization of the tracer method for regional cerebral blood flow (rCBF) measurement. An additional significant objective is the evaluation of the coupling of rCBF and local cerebral glucose utilization (LCGU). In these studies the spectrum of this coupling between metabolism and blood flow will be explored and determinations of the range of validity of the tracer method investigated. Furthermore, tracer kinetics modeling will be developed for these systems. The limited angle positron camera (LAPC) and PETT systems will be utilized, and comparison between positron tomography and computerized autoradiographic analysis will be performed. Substances to be evaluated include 18F-4-fluoroantipyrine, 18F-4-fluoro-2-14C-antipyrine, 2-11C-4-iodoantipyrine, 38K, 19Ne, 77Kr, 18F-2-fluoro-2-deoxy-D-glucose, and 1-11C-deoxy-D-glucose. Initial studies will emphasize serial testing of tracer substances to determine the optimal rCBF indicator. That tracer which demonstrates a maximal partition coefficient and exhibits decay properties most propitious for the instrumentation will be used for coupling studies and to examine blood flow in experimental ischemia. Specific experimental situations include changes of pACO2, halothane effects, hypoxia, alterations of systemic blood pressure, induction of intracranial hypertension, pharmacologic manipulations including phenobarbital and gamma-hydroxybutyrate and its lactone, focal and generalized experimental seizures, hypo- and hyperglycemia, and focal ischemia.